Cumpana Loredana, Zanoletti Olivia, Kankanamge Dinesh, Copits Bryan, Sandi Carmen, Astori Simone
Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Nat Commun. 2025 Aug 19;16(1):7720. doi: 10.1038/s41467-025-63118-6.
Corticotropin-releasing hormone (CRH) is a peptide associated with stress and anxiety that acts as a potent modulator throughout the nervous system. The thalamic reticular nucleus (TRN) displays high expression of the CRH receptor 1 (CRHR1), but whether CRH modulates key TRN functions, such as sleep spindle rhythmogenesis, remained unexplored. Combining polysomnographic and photometric recordings in mice, we show that CRH release in TRN during non-rapid-eye movement sleep (NREMS) oscillates with a ~50-s periodicity, anti-correlating with sleep spindle dynamics. Optogenetic manipulations of CRH release in TRN modulated NREMS fragmentation through microarousals with corresponding changes in sigma and delta power. In ex-vivo recordings, CRHR1 activation decreased the propensity of TRN neurons to fire calcium bursts. CRHR1 knockdown in parvalbumin TRN neurons prevented the effects of CRH on NREMS and TRN bursting. Thus, CRHR1 impacts NREMS by modulating thalamic excitability, providing a potential target to stabilize sleep impairments associated with stress and anxiety.
促肾上腺皮质激素释放激素（CRH）是一种与应激和焦虑相关的肽，在整个神经系统中起强效调节剂的作用。丘脑网状核（TRN）中促肾上腺皮质激素释放激素受体1（CRHR1）表达较高，但CRH是否调节TRN的关键功能，如睡眠纺锤波节律生成，仍未得到探索。结合小鼠的多导睡眠图和光度记录，我们发现非快速眼动睡眠（NREMS）期间TRN中CRH的释放以约50秒的周期振荡，与睡眠纺锤波动态呈反相关。对TRN中CRH释放进行光遗传学操作，通过微觉醒调节NREMS片段化，同时伴随着西格玛和德尔塔功率的相应变化。在离体记录中，CRHR1激活降低了TRN神经元产生钙猝发的倾向。小清蛋白TRN神经元中CRHR1基因敲低可防止CRH对NREMS和TRN爆发的影响。因此，CRHR1通过调节丘脑兴奋性影响NREMS，为稳定与应激和焦虑相关的睡眠障碍提供了一个潜在靶点。
